四类典型全身热疗方法加热效果的理论评估

如何快速有效地提高肿瘤患者体核温度是全身热疗实践中的一个十分重要而困难的课题,但目前对现有的各类全身加热措施尚缺乏明确的认识.本文采用有限元数值计算方法,对接近真实边界条件下的四类典型全身热疗措施进行了理论评估,对比分析了不同加热途径的升温效果,指出了进一步提高加热效率的技术策略.研究结果指出,体内加热方式的加热效果最好,也适合于临床操作,应是今后发展高效全身热疗装备的重点.     

肿瘤热疗无损测温方法的研究进展

肿瘤热疗(hyperthermia)是利用肿瘤组织对温度敏感性高于正常组织的性质,即人体正常细胞在42. 5～43℃下不会受到损伤,但大部分肿瘤细胞在该温度下会被诱导进入凋亡过程。临床上应用超声、微波或红外等作为加热源,加热并杀死肿瘤组织而使得正常组织基本不受损伤。但是对于如何精确测量肿瘤热疗的温度从而控制热疗剂量仍然是一个难题。本文综述了目前肿瘤热疗过程中电阻抗断层成像(ectrical impedance tomograph,EIT)测温、红外热图引导技术、微波辐射测温法、超声无损测温、磁共振成像测温(magnetic resonance imaging,MRI)等无损测温方法及其研究现状,展望了如何有效精确测量肿瘤热疗时的温度,为控制肿瘤热疗的热剂量提供参考,以期在不伤害正常组织的前提下,使肿瘤组织产生不可逆的损伤。     

纳米微粒磁性靶向热疗作用的应用研究(文献综述)

1 热疗及磁性靶向热疗的概念 将肿瘤部位加热到41℃以上治疗恶性肿瘤的方法称热疗（Hyperthermia）。高温治疗肿瘤由来已久,很早就被认为是有效的疗法。近30年来,随着高温设备的不断更新,加热技术、测温技术的不断发展,高温疗法已成为肿瘤治疗的重要手段之一。目前常用的热疗方法如射频、微波、激光、聚焦超声、全身热疗、隔离灌注等,因对肿瘤的靶向能力差,易导致周围组织的温度升高,具有一定的创伤性,其临床应用范围有限。近年来,随着纳米技术的研究进展,在纳米水平上研制纳米磁性微粒作为药物载体又引起了人们的广泛兴趣,磁性微粒不仅可以用作药物载体,而且在交变磁场下还可发热升温,引起了人们对其在肿瘤热疗方面的潜在价值的重视。     

单极子微波热疗天线在生物组织中产生的温度分布的调控

微波热疗的关键是实现微波能量长时间较均匀加热肿瘤组织。采用连续加热方法，在不改变天线结构及插入位置的条件下．很难实现对治疗区域的长时间均匀加热。我们结合电磁场的时域有限差分（Finite Difference Time Domain，FDTD）和温度场的有限差分方法模拟微波热疗天线在生物组织中产生的温度分布，通过调整天线的加热功率，并采用分时间隔加热的治疗方法，实现了微波能量对一定区域组织的长时间较均匀加热。     

基于血管介入式加热的微创性全身热疗方法

全身热疗正逐渐被认为是对已扩散全身的恶性肿瘤实施有效治疗的一种可行途径.但因缺乏简便、微创的机体升温手段,使其尚不能广泛应用于临床.针对这一技术瓶颈,本文建立了崭新的加热探针介入式微创全身热疗方法,通过对大血管直接加热并借助其内血液的输运实现高效的全身加热.并研制了一套模拟血管内加热的全身热疗试验台,系统评估了该方法的加热能力及其对血流动力学参数的影响,而且从理论上分析了新方法的可行性.理论及模拟试验均表明了血管介入式全身热疗方法的优点.最后进一步讨论了新方法中亟待改进的一些问题,展望了其在肿瘤治疗中的应用前景.     

磁性纳米颗粒的产热机制及在肿瘤热疗中的应用

磁热疗是继放射治疗、化学药物治疗后新兴的一种微创肿瘤治疗手段。磁性纳米颗粒在外加磁场下靶向病变部位并积集于此,在交变磁场中磁滞或弛豫产热,使病变部位快速升温。磁热在肿瘤微环境使其发生蛋白质变性、DNA损伤、免疫系统激活等,可在短时间内安全有效地杀死肿瘤细胞。综述磁性纳米颗粒的产热机制,在肿瘤磁热疗中与细胞的相互作用,及与其他肿瘤治疗方式的协同作用,并讨论其对细胞毒性和治疗的副作用。     

医用侵入式微波热疗辐射器

作为一种治疗癌症的有效手段，微波热疗技术目前受到广泛的重视。本文总结了治疗深部组织肿瘤的侵入式微波热疗仪的关键部件微波辐射探头的种类、结构、性能。指出合理设计辐射探头是控制能量沉积方位、温度分布、防止能量泄露、提高微波热疗有效性的关键。     

医用侵入式微波热疗辐射器

作为一种治疗癌症的有效手段，微波热疗技术目前受到广泛的重视，本文总结了治疗深部组织肿瘤的侵入式微波热疗仪的关键部件微波辐射探头的种类结构，性能，指出合理设计辐射探头控制能量沉积方法，温度分布，防止能量泄露，提高微波热疗有效的关键。     

一种监测微波热疗机输出功率变化的方法与装置

目的:针对目前微波热疗机实际输出功率在使用过程中会缓慢衰减,功率测量过程相对复杂等问题,提出了一种新的对微波热疗机实际输出功率进行快速测量的方法,并设计了一套对微波热疗机实际输出功率进行快速监测的装置。方法:利用对称振子天线与截止频率较高的低势垒肖特基二极管组成功率传感器,并将该微波天线置于微波热疗机辐射器前方的某一个固定点,在不同微波功率下测量天线感应、并经过二极管检波后的电压,将得到的功率与电压间的函数关系保存在单片机系统中。利用此函数关系,通过测量二极管检波电压来监测微波热疗机实际输出功率。结果:利用研制的装置,在全功率范围内测量微波热疗机的实际输出功率,测量误差小于5%。结论:微波热疗机的实际输出功率与辐射器前方某固定位置上微波天线感应、并经过二极管检波后得到的电压之间存在一个固定的函数关系。完成该电压与功率的定标后,通过测量二极管检波电压,就可以方便、准确地测量出微波热疗机的输出功率,监测输出功率的变化。这将使技术人员能够及时对微波热疗机输出功率进行修正,从而确保微波热疗剂量的准确性与安全性。     

用射频(Rf)加热治疗器

001 用射频(Rf)加热治疗癌在医学中,采用频率从几兆到微波范围的电磁辐射来治疗癌,其结果是令人鼓舞的。由射频(Rf)产生的热是微弱的,但有时能杀死癌细胞。此外,看来它可以改进肿瘤的其它治疗法。在肿瘤治疗中,这种加热疗法是一个较大的突破,称为超高温(Hyperthermia)疗法或简称为热疗。它是根据这样一个简单的技术:即将全身或     

THE THERMAL EFFECT OF FERRIMAGNETIC RESONANCE AND ITS PROBABLE APPLICATION IN MICROWAVE HYPERTHERMIA IN CANCER THERAPY

To improve microwave hyperthevmia in cancer therapy, the thermal effect of fer-rimagnetic resonance (FMR) during microwave irradiation was studied. Resonant temperatureelevation (RTE) of single crystal grain and polycrystal powder of resonant media was measuredalone and in imitative muscle and egg white and in mice. The results indicated that the RTE produced by FMR could be used to improve penetrationdeepness, heating selectivity and temperature distribution of microwave hyperthermia in cancertreatment. It was expected that the potential function of the FMR heating system would be ex-ploited greatly for cancer therapy, and then magnetically guided microwave hyperthermia thera-py, chemotherapy, radiotherapy and immunotherapy might he combined multiply within this sys-tem by means of the static magnetic field (SMF) and magnetic microcarrier. Limitation of reso-nant heating was also discussed in this paper.     

Research on annihilation of cancer cells by glass-ceramics for cancer treatment with external magnetic field. I. Preparation and cytotoxicity

Ferrimagnetic glass-ceramics were prepared as a heating mediator for hyperthermia in cancer treatment. We prepared glasses in the system 40Fe2O3-30CaO-30SiO2 and precipitated ferrimagnetic crystallites through controlled two-step heat treatment. To improve the heating capability of ferrimagnetic crystallites, i.e., magnetite, generation of other crystalline phases should be prohibited. The addition of each 1% of P2O5 and B2O3 led to lowering the crystallization temperature of magnetite, which was useful to suppress the other crystalline formation. The maximum nucleating and crystal growth rates were 20.47 x 10(6)/mm2 x s at 690 degrees C and 8.125 nm/min(0.5) at 940 degrees C, respectively. After nucleation at 690 degrees C for 60 min prior to crystal growth at 940 degrees C for 2 h, samples exhibited the following properties: crystallite size of 90.5 nm, the maximum volumetric fraction of 31.1%, and saturation magnetization of 100 emu/cm2. The coercive forces were ranged between 382.0 and 388.2 Oe in all heat-treatment conditions. As a result of a preclinical evaluation of biocompatibility by agar diffusion test with L929 cells, both as-quenched and heat-treated glasses could be biocompatible.     

Determination and validation of the actual 3D temperature distribution during interstitial hyperthermia of prostate carcinoma.

To determine the thermal dose of a hyperthermia treatment, knowledge of the three-dimensional (3D) temperature distribution is mandatory. The aim of this paper is to validate an interstitial hyperthermia treatment planning system with which the full 3D temperature distribution can be obtained in individual patients. Within a phase I study, 12 patients with prostate cancer were treated with interstitial hyperthermia using our multi electrode current source interstitial hyperthermia treatment (MECS IHT) system. The temperature distribution was measured from within the heating devices and by additional thermometry. The perfusion level was estimated and the heating implant reconstructed. The steady-state temperature distribution was calculated using our interstitial hyperthermia treatment planning system. The simulated temperature distribution was validated by individually comparing the measured and simulated thermo-sensors, both for the thermometry integrated with the heating applicators and the additional thermometry. The entire procedure was also performed on a no-flow agar-agar phantom. It was shown that the calculated temperature distribution of an individual patient during MECS interstitial hyperthermia is very heterogeneous. The validation indicates that the calculated temperature elevations match the measurements within approximately 1 degrees C. Possible improvements are more precise reconstruction, incorporation of discrete vasculature and using a temperature-dependent, heterogeneous perfusion distribution. Further technical improvements of the MECS-IHT system may also result in better temperature calculations.     

Investigation on Tc tuned nano particles of magnetic oxides for hyperthermia applications

Superparamagnetic as well as fine ferrimagnetic particles such as Fe3O4, have been extensively used in magnetic field induced localized hyperthermia for the treatment of cancer. The magnetic materials with Curie temperature (Tc) between 42 and 50 degrees C, with sufficient biocompatibility are the best candidates for effective treatment such that during therapy it acts as in vivo temperature control switch and thus over heating could be avoided. Ultrafine particles of substituted ferrite Co(1-a)Zn(a)Fe2O4 and substituted yttrium-iron garnet Y3Fe(5-x)Al(x)O12 have been prepared through microwave refluxing and citrate-gel route respectively. Single-phase compounds were obtained with particle size below 100 nm. In order to make these magnetic nano particles biocompatible, we have attempted to coat these above said composition by alumina. The coating of alumina was done by hydrolysis method. The coating of hydrous aluminium oxide has been done over the magnetic particles by aging the preformed solid particles in the solution of aluminium sulfate and formamide at elevated temperatures. In vitro study is carried out to verify the innocuousness of coated materials towards cells. In vitro biocompatibility study has been carried out by cell culture method for a period of three days using human WBC cell lines. Study of cell counts and SEM images indicates the cells viability/growth. The in vitro experiments show that the coated materials are biocompatible.     

Performance characteristics of a helical microwave interstitial antenna for local hyperthermia

A helical microwave antenna has been designed to improve heat deposition by interstitial applicators used for clinical hyperthermia. Iso-specific-absorption-rate (SAR) curves of the helical antenna as well as a conventional monopole antenna were measured and compared in both muscle and brain tissue phantoms. The heating pattern of the helical antenna is more uniform along the length of the antenna which has important implications for multiarray implant configurations.     

A review of hyperthermia combined with radiotherapy/chemotherapy on malignant tumors

Therapeutic hyperthermia is a procedure that involves heating tissues to a higher temperature level, typically ranging from 41 degrees C to 45 degrees C. Its combination with radiotherapy and/or chemotherapy has been performed for many years, with remarkable success in treating advanced and recurrent cancers. The current hyperthermia strategies generally include local, regional, and whole-body hyperthermia, which can be implemented by many heating methods, such as microwave, radiofrequency, laser, and ultrasound. There are several hyperthermic treatment modalities in conjunction with radiotherapy/chemotherapy. Numerous studies have attempted to explain the mechanisms of thermosensitization from radiation and chemotherapy; however, a generalized standard for determining an optimal hyperthermia modality combined with radiotherapy/chemotherapy has not been established, so more research is needed. Fortunately, phase II/III clinical trials have demonstrated that hyperthermia combination therapy is beneficial for local tumor control and survival in patients with high-risk tumors of different types. The aim of this article is to present a comprehensive review of the latest advances in tumor hyperthermia combined with radiotherapy and/ or chemotherapy. We specifically focus on synergistic cellular and molecular mechanisms, thermal dose, treatment sequence, monitoring and imaging, and clinical outcomes of the combination therapy. The role of nanoparticles in sensitization during radio-/chemotherapy is also evaluated. Finally, research challenges and future trends in the related areas are presented.     

Optimization of a beam shaping bolus for superficial microwave hyperthermia waveguide applicators using a finite element method

Temperature inhomogeneity in hyperthermia treatments often limits the total thermal dose that can be delivered to the tumour region. To reduce such inhomogeneities, a prototype dynamically modifiable square array of saline-filled patches which attenuate microwave energy was developed for superficial treatments that use external microwave applicators. The array was situated inside the coupling water bolus that is often used with external applicators. The prototype has been previously tested clinically with promising results. A more complete theoretical analysis of the performance of this new bolus design and improvements to its design by modelling are presented here. The analysis was performed by performing five iterative simulations of the SAR pattern produced inside a tissue structure by a waveguide applicator with a water bolus containing the dynamic patch array attached. Between iterations the patch array configuration was modified in an attempt to improve the ability of the bolus to confine heating to an 'L'-shaped tumour region. These simulations were performed using the finite element method. The steady-state temperature profile was then computed using a finite element method based simulation of heat transfer that assumed a given applicator power level and water bolus temperature. Several iterations of these heat transfer simulations were performed with varying applicator power level and water bolus temperature to improve the confinement of heating to the target region. The analysis showed that the dynamic patch array should be capable of conforming heating to an 'L'-shaped target tumour region while limiting the heating to the surrounding normal tissue to an acceptable level.     

The efficiency of clinical microwave applicators measured by a calorimetric method

When inducing localized hyperthermia for superficial cancer therapy with microwaves there has often been question about the total power output from the applicator. Although specific absorption rates and thermograms are used to obtain localized power distributions and heating patterns, these provide, at best, only an approximation of the total power applied to tissues or phantoms. In this paper a calorimetric technique for obtaining total microwave output power from applicators is described. An experimental apparatus was constructed and it was found to be accurate to approximately +/- 5 W. The power output from four clinical microwave applicators as a function of applied electric power was measured and the efficiency was found to be 40% in average. Along with enhancing quality assurance, the areas of hyperthermia research which may benefit the most from this calorimetric technique are computer modeling and patient treatment planning.     

利用超声回波特征无创监测微波热疗的实验研究

寻找一种合适的方法区别正常组织与坏死组织,是癌微波热疗应用中所面临的重要难题.本研究探讨微波热疗过程中组织回波时域的变化,以寻找合适的参数,无创监测热疗组织状态的变化.在原理分析的基础上设计了实验系统,采用微波介入的加热方式,采集超声回波信号,对变性区域做回波幅值时域积分、幅值平方时域积分(能量)和损伤数字减影积分,并分析它们的变化趋势.实验结果表明:生物组织回波的不同方式积分值与加热过程中的组织变性具有相关性,微波热疗前后组织回波的幅值、能量、不均匀性均有增大的趋势.利用超声背向散射积分和反应不均匀度的参数进行监测,可得到较理想的结果.     

Feasibility of salvage interstitial microwave thermal therapy for prostate carcinoma following failed brachytherapy: studies in a tissue equivalent phantom

Thermal therapy is an experimental treatment to destroy solid tumours by heating them to temperatures ranging from 55 degrees C to 90 degrees C, inducing thermal coagulation and necrosis of the tumour. We are investigating the feasibility of interstitial microwave thermal therapy as a salvage treatment for prostate cancer patients with local recurrence following failed brachytherapy. Due to the electrical and thermal conductivity of the brachytherapy seeds, we hypothesized that the seeds could scatter the microwave energy and cause unpredictable heating. To investigate this, a 915 MHz helical antenna was inserted into a muscle-equivalent phantom with and without brachytherapy seeds. Following a 10 W, 5 s input to the antenna, the temperature rise was used to calculate absorbed power, also referred to as specific absorption rate (SAR). Plane wave models based on Maxwell's equations were also used to characterize the electromagnetic scattering effect of the seeds. In addition, the phantom was heated with 8 W for 5 min to quantify the effect of the seeds on the temperature distribution during extended heating. SAR measurements indicated that the seeds had no significant effect on the shape and size of the SAR pattern of the antenna. However, the plane wave simulations indicated that the seeds could scatter the microwave energy resulting in hot spots at the seed edges. Lack of experimental evidence of these hot spots was probably due to the complex polarization of the microwaves emitted by the helical antenna. Extended heating experiments also demonstrated that the seeds had no significant effect on the temperature distributions and rates of temperature rise measured in the phantom. The results indicate that brachytherapy seeds are not a technical impediment to interstitial microwave thermal therapy as a salvage treatment following failed brachytherapy.